Therapeutic Options for Recurrent Glioblastoma—Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy
<p>Kaplan–Meier survival curves for PFS and OS after surgery for recurrence in the PDT and control groups. (<b>A</b>) Patients in the PDT group showed significantly longer PFS than the patients in the control group (median PFS: PDT 5.7 months, control 2.2 months; <span class="html-italic">p</span> = 0.0043). (<b>B</b>) Patients in the PDT group showed significantly longer OS than the patients in the control group (median OS: PDT 16.0 months, Control 12.8 months; <span class="html-italic">p</span> = 0.031).</p> "> Figure 2
<p>Kaplan–Meier survival curves for PFS and OS after surgery for recurrence in the GBM and LGG groups. (<b>A</b>) The PFS was not significantly different between the GBM and LGG groups (median PFS: GBM 6.3 months, LGG 4.2 months; <span class="html-italic">p</span> = 0.31). (<b>B</b>) The OS was not significantly different between the GBM and LGG groups (median OS: GBM 15.4 months, LGG 18.3 months; <span class="html-italic">p</span> = 0.91).</p> "> Figure 3
<p>HE staining and fluorescence microscopy images of normal brain tissue surrounding the tumor (<b>A</b>,<b>B</b>) and recurrent glioblastoma in contrast-enhanced lesions (<b>C</b>,<b>D</b>). Samples were processed for H&E staining or immunofluorescence examination. The nuclei of the tumor cells were stained with DAPI, and red fluorescence at 640 nm was detected in the tumor cells at an excitation wavelength of 400 nm, which indicated the TS uptake in the tumor and normal brain tissue. Abbreviations: CE, contrast enhanced.</p> "> Figure 4
<p>Fluorescence intensity in CE region of recurrent glioblastoma samples from GBM (<span class="html-italic">n</span> = 14) and LGG (<span class="html-italic">n</span> = 6) groups. There was no significant difference between the two groups (Mann–Whitney U test, <span class="html-italic">p</span> = 0.20). Each box represents the interquartile range, and the median was indicated by a bold line. The ends of the whiskers represented the 10th and 90th percentile.</p> "> Figure 5
<p>Representative Case 1. Contrast-enhanced T1-weighted and FLAIR MR image before (<b>A</b>,<b>B</b>) and after (<b>C</b>,<b>D</b>) the first operation. Contrast-enhanced T1-weighted and FLAIR findings before the second operation with PDT (<b>E</b>,<b>F</b>); 3 days (<b>G</b>,<b>H</b>); 2 weeks (<b>I</b>,<b>J</b>); 2 months (<b>K</b>,<b>L</b>), and 47 months (<b>M</b>,<b>N</b>) after the second surgery.</p> "> Figure 6
<p>Representative Case 2. Contrast-enhanced T1-weighted and FLAIR MR image before (<b>A</b>,<b>B</b>) and after (<b>C</b>,<b>D</b>) the first operation. Contrast-enhanced T1-weighted and FLAIR findings before the second operation with PDT (<b>E</b>,<b>F</b>); 3 days (<b>G</b>,<b>H</b>); 2 weeks (<b>I</b>,<b>J</b>); 2 months (<b>K</b>,<b>L</b>); 5 months (<b>M</b>), and 50 months (<b>O</b>,<b>P</b>) after the second surgery. PET study at 5 months postoperatively (<b>N</b>). The pathological results of the suspected recurrent lesion at 5 months postoperatively showed venous infarction ((<b>Q</b>) arrowhead) and loss of internal elastic membrane ((<b>Q</b>) arrow), but no obvious tumor cells (<b>R</b>).</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Selection and Treatment Criteria
2.2. Intraoperative TS-PDT Protocol
2.3. Neuropathological Analysis
2.4. Evaluation of TS Uptake in Recurrent GBM
2.5. Patient Assessment and Follow-Up
2.6. Statistical Analysis
3. Results
3.1. Patient Demographics and Characteristics
3.2. Patient Safety
3.3. Survival Analysis
3.4. Univariate and Multivariate Analysis
3.5. TS Uptake Comparison
3.6. Representative Cases
- Case 1
- Case 2
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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PDT | Control | p Value | |
---|---|---|---|
No. of patients | 70 | 38 | |
Age | |||
Average (year) ± SD | 46.7 ± 13.3 | 43.4 ± 13.3 | 0.32 |
Median (range) | 43.5 (20–80) | 42 (16–71) | |
Sex | 0.22 | ||
Male | 39 (56%) | 26 (68%) | |
Female | 31 (44%) | 12 (32%) | |
Median preoperative KPS | |||
KPS score (range) | 80 (40–90) | 85 (50–100) | 0.063 |
EOR | 0.37 | ||
GTR | 64 (91.4%) | 36 (94.7%) | |
STR | 4 (5.7%) | 0 | |
PR | 2 (2.9%) | 2 (5.3%) | |
Histopathology of rec. | 1 | ||
GBM | 69 (98.6%) | 38 (100%) | |
Gliosarcoma | 1 (1.4%) | 0 | |
Previous pathology before rec. | |||
GBM | 43 (62.3%) | 16 (42.1%) | 0.071 |
LGG | 26 (37.7%) | 22 (57.9%) | |
IDH mutation | |||
Rate of IDH mutation | 22.9% (16/70) | 39.5% (15/38) | 0.11 |
Mib-1 | |||
Average ± SD | 19.8 ± 12.0 | 23.4 ± 11.4 | 0.11 |
Median (range) | 17.0 (1.6–51.4) | 20.7 (4.0–46.8) | |
MGMT protein expression | 0.73 | ||
High | 15 (23.1%) | 9 (24.3%) | |
Low | 28 (43.1%) | 13 (35.1%) | |
None | 22 (33.8%) | 15 (40.5%) |
Variables | Univariate Analysis | Multivariate Analysis | |||
---|---|---|---|---|---|
Hazard Ratio [95% CI] | p Value | Hazard Ratio [95% CI] | p Value | ||
Age | <55y vs. ≥55y | 1.52 [0.95–2.44] | 0.079 | ||
KPS | <70 vs. ≥70 | 1.70 [1.04–2.77] | 0.035 | 1.82 [1.11–2.99] | 0.017 |
Pre-rec pathol | GBM vs. LGG | 0.76 [0.51–1.15] | 0.2 | ||
IDH | mIDH1 vs. wtIDH1 | 1.42 [0.91–2.23] | 0.13 | ||
PDT | PDT + Surgery vs. Surgery alone | 0.54 [0.35–0.83] | 0.005 | 0.52 [0.34–0.79] | 0.026 |
Variables | Univariate Analysis | Multivariate Analysis | |||
---|---|---|---|---|---|
Hazard Ratio [95% CI] | p Value | Hazard Ratio [95% CI] | p Value | ||
Age | <55y vs. ≥55y | 1.36 [0.80–2.33] | 0.26 | ||
KPS | <70 vs. ≥70 | 1.79 [1.03–3.09] | 0.038 | 1.82 [1.05–3.15] | 0.033 |
Pre-rec pathol | GBM vs. LGG | 1.04 [0.63–1.69] | 0.89 | ||
IDH | mIDH1 vs. wtIDH1 | 1.69 [0.98–2.91] | 0.06 | ||
PDT | PDT + Surgery vs. Surgery alone | 0.57 [0.34–0.96] | 0.034 | 0.56 [0.33–0.94] | 0.029 |
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Kobayashi, T.; Nitta, M.; Shimizu, K.; Saito, T.; Tsuzuki, S.; Fukui, A.; Koriyama, S.; Kuwano, A.; Komori, T.; Masui, K.; et al. Therapeutic Options for Recurrent Glioblastoma—Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy. Pharmaceutics 2022, 14, 353. https://doi.org/10.3390/pharmaceutics14020353
Kobayashi T, Nitta M, Shimizu K, Saito T, Tsuzuki S, Fukui A, Koriyama S, Kuwano A, Komori T, Masui K, et al. Therapeutic Options for Recurrent Glioblastoma—Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy. Pharmaceutics. 2022; 14(2):353. https://doi.org/10.3390/pharmaceutics14020353
Chicago/Turabian StyleKobayashi, Tatsuya, Masayuki Nitta, Kazuhide Shimizu, Taiichi Saito, Shunsuke Tsuzuki, Atsushi Fukui, Shunichi Koriyama, Atsushi Kuwano, Takashi Komori, Kenta Masui, and et al. 2022. "Therapeutic Options for Recurrent Glioblastoma—Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy" Pharmaceutics 14, no. 2: 353. https://doi.org/10.3390/pharmaceutics14020353
APA StyleKobayashi, T., Nitta, M., Shimizu, K., Saito, T., Tsuzuki, S., Fukui, A., Koriyama, S., Kuwano, A., Komori, T., Masui, K., Maehara, T., Kawamata, T., & Muragaki, Y. (2022). Therapeutic Options for Recurrent Glioblastoma—Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy. Pharmaceutics, 14(2), 353. https://doi.org/10.3390/pharmaceutics14020353